HIV/AIDS, tuberculosis (TB), malaria and trypanosomiasis are infectious diseases of major importance to international health causing tremendous disease burdens on populations globally. HIV, the greatest cause of death internationally, is pandemic with fatal outcomes and dim prospects for vaccine prevention. TB, the second greatest cause of death, exists throughout the world and is epidemic in many regions where its prevalence is great and its mortality is common. Malaria and trypanosomiasis cause immense hardship in some of the world's most resource-limited countries. In this proposal seven established and qualifying NIH-funded investigators are joined by 5 other funded investigators to focus research efforts on the treatment or prevention of these 4 major international health problems. To do so, we require robust state-of-the-art LC-MS/MS instrumentation dedicated to detection and quantitation of low picomolar to femtomolar levels of therapeutic anti-infectives. Funding is requested for purchase of one Applied Biosystems API5500 LC-MS/MS system with a Water Acquity UPLC interface with capabilities for electrospray ionization (ESI) and atmospheric pressure chemical ionization (APCI). The addition of this mass spectrometer system will provide adequate access to qualified investigators that currently have either extremely limited or no access to acceptable instrumentation or currently have assay commitments that exceed their capacity. The acquisition cost is $350,350;institutional support for its proper housing and productive use is robust. Quantitative LC-MS/MS multiple reaction monitoring (MRM) techniques will provide critical data related to therapeutic levels, pharmacokinetics and metabolism of anti-infectives employed or being evaluated for these diseases. The availability of the requested instrumentation will provide a substantial increase in sample throughput capacity, will support new research initiatives, will allow the seamless transition from assay development to sample analysis on more than one instrument, and will provide a back-up mechanism that prevents loss of precious clinical samples in the event of an instrument failure. Despite the morbidity, mortality and economic burden of these diseases, which are widely recognized to be enormous, new therapeutic advances often fall to NIH-sponsored academic scientists. The availability of the requested instrument would substantially increase the productivity of these investigators at Johns Hopkins. PUBLIC HEALTH RELEVANCE: The requested API5500 mass spectrometer is needed to support the NIH-funded research of scientists who are working to develop new preventions and treatments for HIV, tuberculosis, malaria and African trypanosomiasis. The availability of this instrument will greatly increase their ability to study new therapeutic approaches in laboratory studies and in clinical trials.